Biologically active proteins, peptides inhibitor

After the early discovery of a tyrosine 0-sulfate residue in bovine fibrinopeptide B, 15 this posttranslational modification which occurs ubiquitously in proteins was also detected in a series of biologically active peptides such as the neurohormones of the gastrin/cholecysto-kinin (CCK) family of peptides, phyllokinin, Leu-enkephalin, and the thrombin inhibitor hirudin listed in Table 1. 

Many biologically active therapeutic agents contain five-membered heterocycles.92 The imidazole ring system is of particular interest since it is a component of histidine and its decarboxylation metabolite histamine. The wide applicability of the imidazole pharmacophore can be attributed to its hydrogen bond donor-acceptor capability as well as its high affinity for metals which are present in many protein active sites (e.g. Zn, Fe, Mg). Furthermore, improved pharmacokinetics and bioavailability of peptide-based protease inhibitors have been observed by replacing an amide bond with an imidazole. 

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